High-throughput metabolomics used to identify potential therapeutic targets of Guizhi Fuling Wan against endometriosis of cold coagulation and blood stasis

Metabolomics is an emerging and robust discipline and involves the comprehensive evaluation of small molecule endogenous metabolites and enables the exploration of the pathogenesis of diseases. For example, endometriosis - a common disease which mostly occurs in women of childbearing age. A cure for endometriosis of cold coagulation and blood stasis (ECB) is highly sought after. This study was conducted to discover the potential biomarkers of ECB and the effective mechanism undertaken by Guizhi Fuling Wan (GFW) in treating ECB in rats. Urinary metabolomics were performed by using UPLC-Q-TOF-MS with pattern recognition methods to evaluate the changes in metabolic profiles and to identify biomarkers for elucidating the mechanism of the treatment of ECB with GFW. The results showed that urinary metabolism in the two groups were distinctly separated on the 28^th day, and a total of 20 differential biomarkers (16 in the positive mode, 4 in the negative mode) were confirmed involving several key metabolic pathways which included phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, glyoxylate and dicarboxylate metabolism, tyrosine metabolism and the citrate cycle. Following the oral administration of GFW, certain pathways were affected; these included the following: phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, glyoxylate and dicarboxylate metabolism, tyrosine metabolism, citrate cycle, steroid hormone biosynthesis, tryptophan metabolism, phenylalanine metabolism, primary bile acid biosynthesis, and aminoacyl-tRNA biosynthesis. This study also demonstrated that the administration of GFW affected the levels of urine endogenous metabolites, thereby laying a foundation for further study of the pharmacodynamical mechanism of GFW.